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Bromocriptine for Patients With Schizophrenia and Impaired Glucose Tolerance
Not Recruiting
Trial ID: NCT03575000
Purpose
This is a multicenter open-label, pilot study to evaluate the safety and tolerability of
bromocriptine, a dopamine D2/D3 receptor and serotonin 5-HT2C receptor agonist, as an adjunct
to preexisting standard-of-care antipsychotic drug (APD) regimens in the management of
APD-associated impaired glucose tolerance (IGT)/insulin resistance (IR). The ultimate aim of
the study team is to evaluate the efficacy of bromocriptine in treating the metabolic
disturbances associated with APDs and the hypothesis is that bromocriptine will be a
well-tolerated, safe, and inexpensive way to ameliorate these metabolic complications and
prevent or delay the onset of type 2 diabetes (T2D). This study will be a small,
short-duration pilot focusing on safety and tolerability. Twenty psychiatrically stable
APD-treated outpatients, at two sites (VA Pittsburgh and Stanford), aged 18 to 60 years old,
with schizophrenia and comorbid IGT will be recruited and receive 6 weeks of bromocriptine
(flexibly titrated, 2.5-5.0 mg PO daily). Key inclusion criteria are: 1) currently being
treated with second generation APDs for 3 or more months with no change in dose in the 1
month prior to enrollment, 2) fasting glucose 100 to 125mg/dL and/or hemoglobin A1c (HbA1c)
5.7-6.4%. Key exclusions are: 1) prior APD nonadherence, 2) drug/alcohol abuse in the 3
months prior to screening, 3) a history of violent behavior/psychoses, 4) pregnancy, or 5) a
diagnosis of diabetes. Subjects on other dopamine agonists or on medications that may
interact with bromocriptine and those taking corticosteroids or other medications that may
alter glucose levels will be excluded. The purposes of the study are to demonstrate
safety/tolerability, demonstrate feasibility, provide proof of concept, and provide an
open-label assessment of the metabolic and psychiatric effects of bromocriptine in patients
with schizophrenia treated with APDs. The primary metabolic outcome measures will be change
in IR as measured by the HOMA-IR and change in IGT measured by HbA1c. Secondary metabolic
outcome measures include body weight, fasting lipids, and prolactin. The specific aims are as
follows: Specific aim 1: To establish the safety and tolerability of bromocriptine in
patients with schizophrenia and IGT/IR treated with APDs. Specific aim 2: To demonstrate
feasibility/proof of concept for an improvement in APD-induced IGT/IR with bromocriptine.
Official Title
Open-label, Flexible-dose Adjunctive Bromocriptine for Patients With Schizophrenia and Impaired Glucose Tolerance
Stanford Investigator(s)
Jacob S. Ballon
Associate Professor of Psychiatry and Behavioral Sciences (General Psychiatry and Psychology)
Eligibility
Inclusion Criteria:
1. Adult males and females, 18-65 years of age, diagnosed with schizophrenia
2. Female participants must test negative for pregnancy at the time of enrollment based
on a urine pregnancy test and agree to use a reliable method of birth control (e.g.,
oral contraceptives, birth control diaphragms with contraceptive jelly, cervical caps
with contraceptive jelly, condoms with contraceptive foam, intrauterine devices,
partner with vasectomy, or abstinence) until the study is complete.
3. Be treated with FDA-approved second generation antipsychotic medication for at least 3
months, with no change in dose in the 1 month prior to enrollment.
4. Either fasting glucose of 100 to 125 mg/dL inclusive and/or an A1C in the range
between 5.7-6.4%
5. Body mass index at least 30 kg/m2 at screening visit.
6. Negative urine drug screen at screening visit and baseline (week 0) visit
7. Subject must be willing to provide contact information for a close family member or
friend that will contact the study team if the participant exhibits signs of
psychological deterioration
8. Subject's primary mental health provider concurs that study enrollment is acceptable
9. Screening ECG QTc check must be <500ms
10. PANSS score
Exclusion Criteria:
1. History of documented APD non-adherence in prior 3 months.
2. Historical or current diagnosis of diabetes mellitus (type 1, type 2, or other)
3. Pregnant or breast feeding. Women of child-bearing potential must be
surgically-sterile or using reliable methods of birth control.
4. May not have used oral or parenteral systemic corticosteroids within 3 months prior to
study enrollment or have expected use during the course of the study. The use of
either inhaled or topical corticosteroids are not exclusion criteria.
5. May not be taking any antidiabetic/antihyperglycemic medications (e.g., metformin,
sulfonylureas, thiazolidinediones, insulin, DPP-IV inhibitors, SGLT-2 inhibitors,
etc.) currently or within 4 months prior to study enrollment.
6. May not be taking any of the following cytochrome P450 3A4 (CYP3A4) inhibitors:
protease inhibitors (atazanavir, boceprevir, darunavir, fosamprenavir, indinavir,
lopinavir, nelfinavir, ritonavir, saquinavir, telaprevir); certain
antibiotics/antifungals (clarithromycin, erythromycin, telithromycin, chloramphenicol,
ciprofloxacin, fluconazole, itraconazole, ketoconazole, posaconazole, voriconazole);
nefazodone; aprepitant; imatinib; certain calcium channel blockers (diltiazem,
verapamil); Valerian; or grapefruit/grapefruit juice.
7. May not be taking or have sensitivity to any dopamine agonist medications (e.g.,
bromocriptine, cabergoline, pramipexole,ropinirole, rotigotine, etc.) currently or
within 3 months prior to study enrollment.
8. May not be taking or have any sensitivity to any other ergot alkaloids (e.g.,
dihydroergotamine, ergotamine)
9. PANSS score >90, which is equivalent to "moderately ill"
10. Any current hepatic or renal disease
11. QTc of >500ms on screening ECG
12. Any documented history of violent behavior
Intervention(s):
drug: Bromocriptine
Not Recruiting
Contact Information
Stanford University
School of Medicine
300 Pasteur Drive
Stanford,
CA
94305